For Jules Verne it was the friend who keeps us waiting. For Edgar Allan Poe so many little slices of death. But though the reason we spend a third of our lives asleep has so far resisted scientific explanation, research into the impact of sleepless nights on brain function has shed new light on the mystery - and also offered intriguing clues to potential new treatments for depression.
In a study published on Tuesday, researchers show for the first time that sleep resets the steady build-up of connectivity in the human brain which takes place in our wakeful hours. The process appears to be crucial for our brains to remember and learn so we can adapt to the world around us.
The loss of a single night’s sleep was enough to block the brain’s natural reset mechanism, the scientists found. Deprived of rest, the brain’s neurons seemingly became over-connected and so muddled with electrical activity that new memories could not be properly laid down.
But Christoph Nissen, a psychiatrist who led the study at the University of Freiburg, is also excited about the potential for helping people with mental health disorders. One radical treatment for major depression is therapeutic sleep deprivation, which Nissen believes works through changing the patient's brain connectivity. The new research offers a deeper understanding of the phenomenon which could be adapted to produce more practical treatments.
“Why we sleep is a fundamental question. Why do we spend so much of our lives in this brain state? This work shows us that sleep is a highly active brain process and not a waste of time. It’s required for healthy brain function,” said Nissen.
The results are a boost for what is called the synaptic homeostasis hypothesis of sleep, which was developed by scientists at the University of Wisconsin-Madison in 2003. It explains why our brains need to rest after a day spent absorbing all manner of information, from the morning news and the state of the weather, to a chat over lunch and what we must buy for tea.
Known more simply as SHY, the hypothesis states that when we are awake, the synapses that form connections between our brain cells strengthen more and more as we learn and eventually saturate our brains with information. The process requires a lot of energy, but sleep allows the brain to wind down its activity, consolidate our memories, and be ready to start again the next morning.
Writing in the journal Nature Communications, Nissen describes a series of tests that 11 men and nine women aged 19 to 25 took part in, either after a good night's sleep, or after a night without sleep.
On the sleepless night, participants played games, went for walks and cooked food, but were not allowed caffeine. Staff watched them throughout to make sure they stayed awake.
In the first round of experiments, Nissen used magnetic pulses to make neurons fire in the volunteers’ brains and cause a muscle in the left hand to twitch.
When sleep deprived, far weaker pulses were sufficient to make the muscles move. This implied that sleepless brains are in a more excitable state, with their neurons more strongly connected than they are after a good night’s sleep.
Nissen next turned to another form of brain stimulation to mimic the way neurons fire when memories are laid down. He found it harder to get the neurons to respond in sleep-deprived people, a sign that the process of writing memories was impaired by sleep loss.
Taken together, the results suggest that sleep allows the brain to calm its activity so memories can be written down. In contrast, the sleep-deprived brain becomes noisy with electrical activity and so feeble at laying down memories that the process is all but blocked.
The consequences of sleep loss were clear in a simple memory test, with tired volunteers faring worse than those who were well-rested.
Teasing out how sleep affects brain connections could do more than answer why we snooze so much. Shift workers and military personnel that have to cope with sleep deprivation could benefit from new drugs or countermeasures that restore normal brain connectivity. Blood samples taken from volunteers in the study showed that sleep deprivation lowered levels of a molecule called BDNF, or brain-derived neurotrophic factor, which regulates synaptic connections in the brain.
But Nissen is more excited about the study’s implications for understanding therapeutic sleep deprivation and its impact on depression. “If you deprive people with major depression of sleep for one night, about 60 per cent show a substantial improvement in mood, motivation and cognitive function. We think it works by shifting these patients into a more favourable state,” he said.
Though striking when it works, therapeutic sleep deprivation is not much use because many patients relapse after the subsequent night’s sleep. But that is not the point, Nissen says.
“It proves that it’s possible to shift a person’s mood from one state to another within hours. The idea is that we use sleep and sleep deprivation to understand the brain and develop new treatments. If you think about antidepressants or psychotherapy, it can take weeks or months to see any effects.”
Giulio Tononi, a professor of sleep medicine who first proposed SHY at the University of Wisconsin-Madison, said the new study was "truly elegant and powerful" and confirmed experiments that until now had only been performed in animals.
“Sleep is essential, and one main reason is that it allows the brain to learn new things every day while preserving and consolidating the old memories,” Tononi said. “Learning and memory require synaptic activity, which is very energetically expensive and prone to saturation. Sleep allows the brain to renormalize this synaptic activity after it increases in the waking day.”
Lars Westlye, a psychologist at University of Oslo, called the study "wonderful" and said the results could throw light on links between the biology of sleep, more complex brain functions, and severe mental disorders such as schizophrenia and depression. Like Nissen he believes that a clearer understanding of brain connectivity might explain why sleep deprivation can be so effective in people with depression, and plans to study the effect in patients.
“These new results should strongly motivate further studies in patient groups, both to learn more about the roots of the disorders and how to treat them,” Westlye said.